Is TRAPPC2 p.Arg35His (c.104G>A) pathogenic?

TRAPPC2 p.Arg35His (c.104G>A) is classified Uncertain significance in TRAPPC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-08). AlphaMissense: likely benign (0.3199); Ultra-rare (popmax 0.0109%, amr); Associated with Inborn genetic diseases.

What condition is associated with TRAPPC2 p.Arg35His (c.104G>A)?

TRAPPC2 p.Arg35His (c.104G>A) is associated with Inborn genetic diseases (ClinVar).

How common is TRAPPC2 p.Arg35His (c.104G>A) in the general population?

TRAPPC2 p.Arg35His (c.104G>A) is ultra-rare (popmax 0.0109%, amr) (gnomAD).

What do computational predictors say about TRAPPC2 p.Arg35His (c.104G>A)?

AlphaMissense predicts likely benign (score 0.3199) — an in-silico prediction, not a clinical call.

TRAPPC2 p.Arg35His

c.104G>A · rs756056537 · VCV2300474

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3199 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0109%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3199	likely benign
REVEL	0.679	pathogenic-leaning
SaProt	LLR -8.98	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 2.2	GERP 2.4, phastCons 0.98
Regional constraint	o/e 0.48	unconstrained · MANE · 5,553 bp · p 5.3e-08 · regional, not allelic
Overall
CADD	22.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0109% Admixed American · 5/45,992 alleles

Filtering AF 0.00426% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0027%

Overall 0.000456% 5/1,097,575 alleles · ultra-rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: TRAPPC2
Protein: p.Arg35His
Coding: c.104G>A
MANE Select: NM_003611 · reported on NM_001011658
dbSNP: rs756056537
Type: single nucleotide variant
Location: chrX:13716668 (GRCh38)

Full TRAPPC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/trappc2-p-arg35his (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown